High Dose Chemo With Stem Cell Transplant as Treatment for Multiple Sclerosis That Failed Prior Treatment

This study has been terminated.
(Insufficient accruals; PI leaving site)
Sponsor:
Information provided by (Responsible Party):
Seah Lim M.D., Texas Oncology Cancer Center
ClinicalTrials.gov Identifier:
NCT01679041
First received: August 29, 2012
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to evaluate the toxicity and the effectiveness of high dose chemotherapy with HPC transplant Multiple Sclerosis that has failed at least two lines of therapy


Condition Intervention Phase
Multiple Sclerosis
Drug: Alemtuzumab
Drug: Fludarabine
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of High Dose Chemotherapy With Autologous Hematopoietic Progenitor Cell Transplant for Multiple Sclerosis That Failed at Least Two Lines of Therapy

Resource links provided by NLM:


Further study details as provided by Texas Oncology Cancer Center:

Primary Outcome Measures:
  • To evaluate the toxicity of autologous HPC transplant in patients with multiple sclerosis that have failed at least two lines of disease modifier therapy [ Time Frame: At 5 years post transplant ] [ Designated as safety issue: Yes ]
    All follow-up appointments will be carried out at Texas Oncology-Amarillo Cancer Center. Patients will be monitored for clinical toxicities and using laboratory blood tests for renal functions, hepatic functions, and bone marrow functions at At discharge post-transplant, then again at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that 6 monthly until death..


Secondary Outcome Measures:
  • To evaluate the effectiveness of high dose chemotherapy with HPC transplant for multiple sclerosis sclerosis that has failed at least two lines of therapy [ Time Frame: Assessed at baseline, tat 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death ] [ Designated as safety issue: No ]
    hen rechecked Neurologic evaluations will be carried out in the offices of the two neurology co-Investigators and the information provided to the transplant physicians for record. Patient will also undergo a repeat MRI scan at 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death, after the transplant to evaluate changes in the number of MS plaques. Subsequent MRI scan will be determined by the patient's neurologist as is needed clinically.


Enrollment: 1
Study Start Date: November 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
Conditioning regimens with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients.
Drug: Alemtuzumab
Alemtuzumab 10 mg given IV on day 1 of the 5 day conditional regimen
Drug: Fludarabine
Fludarabine 25mg/m2 daily given IV on days 1-5 of the 5 day conditioning regimen
Drug: Cyclophosphamide
Cyclophosphamide is given 3 gm/m2 for mobilization, and then repeated during 5 day conditioning regimen w/ doses of 50mg/kg/day on days 1-4

Detailed Description:

Multiple sclerosis is an inflammatory autoimmune disease characterized by loss of myelin and axonal damage, having typical contrast-enhanced MRI foci as an imaging counterpart. MS shows three main patterns of clinical course: relapsing/remitting, primary progressive and secondary progressive.Concerning disease pattern, secondary progressive is the standard indication, to avoid overtreatment in relapsing/remitting patients or ineffectual treatment in primary relapsing patients.

Currently, MS is the most common autoimmune disease that have been treated with autologous HPC transplants (Fagius et al, 2009; Burt et al, 2009; Saccardi et al, 2006). More than 350 consecutive cases have been reported by the EBMT over the last decade. Most patients who underwent autologous HPC transplant for MS in the early studies had secondary progressive MS, and relatively fewer had relapsing remitting disease, with a Kurtzke Expanded Disability Status Scale (EDSS) of 3.0-9.5 at the time of transplant. Significant objective and subjective improvements have been reported in up to 70% of these patients.

The following conditioning regimens will be used, with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients. Prophylaxis of Acyclovir, Levaquin, and Fluconazole will be given to prevent infections. The autologous HPC will be infused within 48-72 hours of completing the chemotherapy. The patients will receive additional supportive care medications and treatments as necessary. Neutrophil engraftment will be defined as the day on which the ANC rises to > 500 cells/ml for two consecutive days. Platelet engraftment will be defined as the first day on which the platelet count rises to > 20,000/ml over a 7-day interval without transfusion support.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Age between 18-60, inclusive

Patients carry a diagnosis of multiple sclerosis, according to the McDonald's criteria for diagnosis (Polman et al, 2011).

Must have a neurologist providing the primary care for the MS and be willing to be evaluated for the multiple sclerosis by the two neurologists who are the co-investigators in the protocol.

Must be documented to be HIV negative.

An EDSS of 3.5 - 5.5

Patients must be able to give written consent.

Inflammatory disease despite primary disease modifying therapy with at least 6 months of interferon and another disease modifying therapy, including fingolimod,glativamir, natalizumab, and mitoxantrone. Failure is defined as two or more clinical relapses with documented neurologic changes (excluding sensory changes) within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids). Failure may also be defined as one relapse (excluding sensory changes) treated with methylprednisone and, on a separate occasion within the previous 12 months, evidence of active inflammation (i.e. gadolinium enhancement on MRI scan of the CNS).

No previous history of allergic reaction to cyclophosphamide, G-CSF or mesna

Patients must not be pregnant

Failure to accept or comprehend irreversible sterility as a potential side effect of therapy.

Life expectancy of more than 6 months

No evidence of myelodysplastic syndrome on peripheral blood smear

Not allergic to cyclophosphamide, mesna, fludarabine or alemtuzumab

Baseline serum creatinine must be <1.5 mg/dL, left ventricular ejection fraction >55%, adequate pulmonary functions (oxygen saturation at room air of >90%), and AST and ALT not > 2x upper limits of normal, and no history of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma in situ of the cervix.

Exclusion Criteria:

Diagnosis of primary progressive MS.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01679041

Locations
United States, Texas
Texas Oncology
Amarillo, Texas, United States, 79106
Dr Ruby Saulog
Amarillo, Texas, United States, 79106
Amarillo Diagnostic Clinic
Amarillo, Texas, United States, 79106
Sponsors and Collaborators
Seah Lim M.D.
Investigators
Principal Investigator: Seah Lim, MD Texas Oncology
  More Information

Publications:
Pasquini, MC, Griffith, LM, Arnold, DL, et al. Hematopoietic stem cell transplantation for multiple sclerosis: collaboration of the CIBMTR and EBMT to facilitate international clinical studies. Biol Blood Marrow Transplant. 2010;16:1076-83.

Responsible Party: Seah Lim M.D., Sponsor-Principal Investigator (MD), Texas Oncology Cancer Center
ClinicalTrials.gov Identifier: NCT01679041     History of Changes
Other Study ID Numbers: 20112015
Study First Received: August 29, 2012
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 28, 2014